{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:46:16Z","timestamp":1791179176634,"version":"4.1.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2003,7,1]],"date-time":"2003-07-01T00:00:00Z","timestamp":1057017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Constitutive activation of the NF-\u03baB has been documented to be involved in the pathogenesis of many human malignancies, including hemopoietic neoplasms. In this study, we examined the status of NF-\u03baB in two non-Hodgkin\u2019s lymphoma cell lines derived from mantle cell lymphoma (MCL) samples and in patient MCL biopsy specimens by EMSA and confocal microscopic analysis. We observed that NF-\u03baB is constitutively activated in both the MCL cell lines and in the MCL patient biopsy cells. Since NF-\u03baB has been shown to play an important role in a variety of cellular processes, including cell cycle regulation and apoptosis, targeting the NF-\u03baB pathways for therapy may represent a rational approach in this malignancy. In the MCL cell lines, inhibition of constitutive NF-\u03baB by the proteasome inhibitor PS-341 or a specific pI\u03baB\u03b1 inhibitor, BAY 11-7082, led to cell cycle arrest in G1 and rapid induction of apoptosis. Apoptosis was associated with the down-regulation of bcl-2 family members bcl-xL and bfl\/A1, and the activation of caspase 3, that mediates bcl-2 cleavage, resulting in the release of cytochrome c from the mitochondria. PS-341or BAY 11-induced G1 cell cycle arrest was associated with the inhibition of cyclin D1 expression, a molecular genetic marker of MCL. These studies suggest that constitutive NF-\u03baB expression plays a key role in the growth and survival of MCL cells, and that PS-341 and BAY 11 may be useful therapeutic agents for MCL, a lymphoma that is refractory to most current chemotherapy regimens.<\/jats:p>","DOI":"10.4049\/jimmunol.171.1.88","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:28:08Z","timestamp":1398022088000},"page":"88-95","source":"Crossref","is-referenced-by-count":276,"title":["Inhibition of Constitutive NF-\u03baB Activation in Mantle Cell Lymphoma B Cells Leads to Induction of Cell Cycle Arrest and Apoptosis"],"prefix":"10.1093","volume":"171","author":[{"given":"Lan V","family":"Pham","sequence":"first","affiliation":[{"name":"Department of Hematopathology, University of Texas M. D. Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archito T","family":"Tamayo","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, University of Texas M. D. Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda C","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, University of Texas M. D. Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piao","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, University of Texas M. D. Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, University of Texas M. D. 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